Cephalosporin compounds

ABSTRACT

The present invention relates to new cephalosporin compounds of the formula (I), particularly 3-position of cephem rings thereof substituted with new thione compounds and pharmaceutically acceptable salts thereof, which have broad antibacterial activities against both Gram-positive and Gram-negative bacteria, and the said compounds can be prepared by reacting the compounds of the formula (II) with the new thione compounds of the formula (III). ##STR1## wherein R 1  is a C 1-4  alkyl(preferably methyl or ethyl), C 3-4  alkenyl(preferably allyl), C 3-4  alkynyl (preferably propargyl) group or --C(R a ) (R b )CO 2  H(preferably --C(CH 3 ) 2  CO 2  H or --CH 2  CO 2  H), wherein R 1  and R b , same or different, are a hydrogen atom or a C 1-4  alkyl group; 
     R 2  is a C 1-4  alkyl(preferably methyl or ethyl), C 3-4  alkenyl(preferably allyl), C 3-4  cycloalkyl(preferably cyclopropyl) group or carboxyalkyl(preferably --CH 2  CO 2  H) group; 
     R 3  is a 5- or 6-membered heterocyclic compound-containing 1 or 2 nitrogen atom(s) (preferably piperazine, alkylpiperazine-substituted with C 1-4  alkyl at N-- or 2-position of piperazine, imidazole-substituted or unsubstituted with C 1-4  alkyl); R 4  is hydrogen or a carboxylic acid.

This application is a 35 USC §371 of PCT/KR93/0005, filed Jan. 16, 1993.

This application is a 35 USC §371 of PCT/KR93/0005, filed Jan. 16, 1993.

FIELD OF THE INVENTION

The present invention relates to new cephalosporin compounds of theformula (I), particularly 3-position of cephem rings substituted withnew thione compounds and pharmaceutically acceptable salts thereof,which have broad antibacterial activities against both Gram-positive andGram-negative bacteria.

SUMMARY OF THE INVENTION

An objective of the present invention is to provide new antibioticcephalosporin compounds of the formula(I) or pharmaceutically acceptablesalts thereof ##STR2## wherein R₁ is a C₁₋₄ alkyl (preferably ethyl orethyl), C₃₋₄ alkenyl(preferably allyl), C₃₋₄ alkynyl (preferablypropargyl) group or --C(R^(a))(R^(b))CO₂ H(preferably --C(CH₃)₂ CO₂ H or--CH₂ CO₂ H), wherein R^(a) and R^(b), same or different, are a hydrogenatom or a C₁₋₄ alkyl group;

R₂ is a C₁₋₄ alkyl (preferably methyl or ethyl), C₃₋₄ alkenyl(preferably allyl), C₃₋₄ cycloalkyl (preferably cyclopropyl)group orcarboxyalkyl (preferably --CH₂ CO₂ H)group;

R₃ is a 5- or 6-membered heterocyclic compounds-containing 1 or 2nitrogen atom(s) (preferably piperazine, alkylpiperazine-substitutedwith C₁₋₄ alkyl at N-- or 2-position of piperazine,imidazole-substituted or unsubstituted with C₁₋₄ alkyl);

R₄ is hydrogen or a carboxylic acid.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of the formula(I) can be prepared by reacting thecompounds of the formular(II) with the new thione compounds of theformular (III), as follows: ##STR3## wherein R₁ is a methyl, allyl,propargyl group or --C(CH₃)₂ CO₂ H;

R₂,R₃ and R₄ are the same as defined above.

In the preparation of the objective compounds(I), the compounds of theformula(III) are used preferably in an amount of from 1 to 2equivalent(s) based on 1 equivalent of the compounds of the formula(II).The reaction for introducing the compounds(lII) into the 3-position ofcompound(II) to prepare compounds(I) is carried out in the presence of asolvent such as water, N,N-dimethylformamide, dimethylsulfoxide, or amixed agueous solvent of water. An appropriate water-miscible solvent isacetonitrile or acetone.

Also, the reaction may be carried out at 40° C. to 100° C., preferably60° C. to 80° C.

To stabilize reaction products and their intermediates, one or moresalts selected from the group consisting of sodium iodide and potassiumiodide can be used as stabilizing agents.

On the other hand, the separation and purification of the compounds(I)can be carried out using a known method such as recrystallization,column chromatography over silica gel or ion-exchange chromatography.

The new thione compounds of the formula(III) can be prepared fromquinolone compounds which prepared by known method, as follows: ##STR4##wherein R₂ is a methyl cyclopropyl, ethyl or allyl group;

R₄ is hydrogen;

R₃ is the same as defined above.

The compounds of the formula(IV) can be prepared by reacting quinolonecompounds, sodium borohydride with p-toluenesulfonic acid in the polarsolvent, preferably alcohol.

The compounds of the formula(V) can be prepared by reacting thecompounds of the formular(IV) with p-chloranil in the polar solvent,preferably 1,4-dioxane at 50° C. to 100° C.

Also, the compounds of the formula(VI) can be prepared by reacting thecompounds of the formular(V) with phosphorus pentasulfide in the polarsolvent, preferably acetonitrile, and the new thione compounds of theformula(III) can be prepared by substitution of 5- or 6-memberedheterocyclic compounds-containing 1 or 2 nitrogen atom(s)(preferablypiperazine, alkylpiperazine-substituted with C₁₋₄ alkyl at N-- or2-position of piperazine, imidazole-substituted or unsubstituted withC₁₋₄ alkyl) at the 7-position of compounds(VI).

In case R₄ is a carboxylic acid, the compounds of the formula(III) canbe prepared from the compounds of the formula(VII) which prepared byknown method, as follows: ##STR5## wherein R₂ is a cyclopropyl;

R₄ is a carboxylic acid;

R₃ is the same as defined above.

The compounds of the formula(VIII) can be prepared by reacting with thecompounds of the formular(VII) and phosphorus pentasulfide in the polarsolvent, preferably acetonitrile.

The compounds of the formula(IX) can be prepared by hydrolysis of thecompounds(VIII).

Also, the compounds of the formula(III) can be prepared by substitutionof 5-or 6-membered heterocyclic compounds-containing 1 or 2 nitrogenatom(s) (preferably piperazine, alkylpiperazine-substituted with C₁₋₄alkyl at N-- or 2-position of piperazine, imidazole-substituted orunsubstituted with C₁₋₄ alkyl) at the 7-position of compounds(IX).

The new thione compounds of the formula(III) are shown in Table 1.

                  TABLE 1                                                         ______________________________________                                        New Thione Compounds                                                           ##STR6##                                                                     Compound No.                                                                             R.sub.2    R.sub.3       R.sub.4                                   ______________________________________                                        III-1      Methyl     Piperazine    H                                         III-2      Methyl     N-Methylpiperazine                                                                          H                                         III-3      Methyl     1-Ethylpiperazine                                                                           H                                         III-4      Methyl     2-Methylpiperazine                                                                          H                                         III-5      Methyl     Imidazole     H                                         III-6      Methyl     4-Methylimidazole                                                                           H                                         III-7      Cyclopropyl                                                                              Piperazine    H                                         III-8      Cyclopropyl                                                                              N-Methylpiperazine                                                                          H                                         III-9      Cyclopropyl                                                                              1-Ethylpiperazine                                                                           H                                         III-10     Cyclopropyl                                                                              2-Methylpiperazine                                                                          H                                         III-11     Cyclopropyl                                                                              Imidazole     H                                         III-12     Cyclopropyl                                                                              4-Methylimidazole                                                                           H                                         III-13     Cyclopropyl                                                                              1-Ethylpiperazine                                                                           COOH                                      III-14     Cyclopropyl                                                                              2-Methylpiperazine                                                                          COOH                                      III-15     Ethyl      Piperazine    H                                         III-16     Ethyl      N-Methylpiperazine                                                                          H                                         III-16     Ethyl      N-Methylpiperazine                                                                          H                                         III-17     Ethyl      1-Ethylpiperazine                                                                           H                                         III-18     Ethyl      2-Methylpiperazine                                                                          H                                         III-19     Allyl      Piperazine    H                                         III-20     Allyl      N-Methylpiperazine                                                                          H                                         III-21     Allyl      1-Ethylpiperazine                                                                           H                                         III-22     Allyl      2-Methylpiperazine                                                                          H                                         ______________________________________                                    

The new cephalosporin compounds of the formula(I) are shown in Table 2.

                                      TABLE 2                                     __________________________________________________________________________    New Cephalosporin Compounds                                                    ##STR7##                                                                     Compound No.                                                                          R.sub.1  R.sub.2 R.sub.3    R.sub.4                                   __________________________________________________________________________    I-1     CH.sub.3 Methyl  Piperazine H                                         I-2     CH.sub.3 Methyl  N-Methylpiperazine                                                                       H                                         I-3     CH.sub.3 Methyl  1-Ethylpiperazine                                                                        H                                         I-4     CH.sub.3 Methyl  2-Methylpiperazine                                                                       H                                         I-5     CH.sub.3 Cyclopropyl                                                                           Piperazine H                                         I-6     CH.sub.3 Cyclopropyl                                                                           N-Methylpiperazine                                                                       H                                         I-7     CH.sub.3 Cyclopropyl                                                                           1-Ethylpiperazine                                                                        H                                         I-8     CH.sub.3 Cyclopropyl                                                                           2-Methylpiperazine                                                                       H                                         I-9     CH.sub.3 Ethyl   Piperazine H                                         I-10    CH.sub.3 Ethyl   N-Methylpiperazine                                                                       H                                         I-11    CH.sub.3 Ethyl   1-Ethylpiperazine                                                                        H                                         I-12    CH.sub.3 Ethyl   2-Methylpiperazine                                                                       H                                         I-13    CH.sub.3 Allyl   Piperazine H                                         I-14    CH.sub.3 Allyl   N-Methylpiperazine                                                                       H                                         I-15    CH.sub.3 Allyl   1-Ethylpiperazine                                                                        H                                         I-16    CH.sub.3 Allyl   2-Methylpiperazine                                                                       H                                         I-17    CH.sub.3 Methyl  Imidazole  H                                         I-18    CH.sub.3 Methyl  4-Methylimidazole                                                                        H                                         I-19    CH.sub.3 Cyclopropyl                                                                           Imidazole  H                                         I-20    CH.sub.3 Cyclopropyl                                                                           4-Methylimidazole                                                                        H                                         I-21    CH.sub.2 CHCH.sub.2                                                                    Methyl  Piperazine H                                         I-22    CH.sub.2 CHCH.sub.2                                                                    Methyl  N-Methylpiperazine                                                                       H                                         I-23    CH.sub.2 CHCH.sub.2                                                                    Methyl  1-Ethylpiperazine                                                                        H                                         I-24    CH.sub.2 CHCH.sub.2                                                                    Methyl  2-Methylpiperazine                                                                       H                                         I-25    CH.sub.2 CHCH.sub.2                                                                    Cyclopropyl                                                                           Piperazine H                                         I-26    CH.sub.2 CHCH.sub.2                                                                    Cyclopropyl                                                                           N-Methylpiperizine                                                                       H                                         I-27    CH.sub.2 CHCH.sub.2                                                                    Cyclopropyl                                                                           1-Ethylpiperazine                                                                        H                                         I-28    CH.sub.2 CHCH.sub.2                                                                    Cyclopropyl                                                                           2-Methylpiperazine                                                                       H                                         I-29    CH.sub.2 CHCH.sub.2                                                                    Ethyl   Piperazine H                                         I-30    CH.sub.2 CHCH.sub.2                                                                    Ethyl   N-Methylpiperazine                                                                       H                                         I-31    CH.sub.2 CHCH.sub.2                                                                    Ethyl   1-Ethylpiperazine                                                                        H                                         I-32    CH.sub.2 CHCH.sub.2                                                                    Ethyl   2-Methylpiperazine                                                                       H                                         I-33    CH.sub.2 CHCH.sub.2                                                                    Allyl   Piperazine H                                         I-34    CH.sub.2 CHCH.sub.2                                                                    Allyl   N-Methylpiperazine                                                                       H                                         I-35    CH.sub.2 CHCH.sub.2                                                                    Allyl   1-Ethylpiperazine                                                                        H                                         I-36    CH.sub.2 CHCH.sub.2                                                                    Allyl   2-Methylpiperazine                                                                       H                                         I-37    CH.sub.2 CCH                                                                           Methyl  Piperazine H                                         I-38    CH.sub.2 CCH                                                                           Methyl  N-Methylpiperazine                                                                       H                                         I-39    CH.sub.2 CCH                                                                           Methyl  1-Ethylpiperazine                                                                        H                                         I-40    CH.sub.2 CCH                                                                           Methyl  2-Methylpiperazine                                                                       H                                         I-41    CH.sub.2 CCH                                                                           Cyclopropyl                                                                           Piperazine H                                         I-42    CH.sub.2 CCH                                                                           Cyclopropyl                                                                           N-Methylpiperazine                                                                       H                                         I-43    CH.sub.2 CCH                                                                           Cyclopropyl                                                                           1-Ethylpiperazine                                                                        H                                         I-44    CH.sub.2 CCH                                                                           Cyclopropyl                                                                           2-Methylpiperazine                                                                       H                                         I-45    CH.sub.2 CCH                                                                           Ethyl   Piperazine H                                         I-46    CH.sub.2 CCH                                                                           Ethyl   N-Methylpiperazine                                                                       H                                         I-47    CH.sub.2 CCH                                                                           Ethyl   1-Ethylpiperazine                                                                        H                                         I-48    CH.sub.2 CCH                                                                           Ethyl   2-Methylpiperazine                                                                       H                                         I-49    CH.sub.2 CCH                                                                           Allyl   Piperazine H                                         I-50    CH.sub.2 CCH                                                                           Allyl   N-Methylpiperazine                                                                       H                                         I-51    CH.sub.2 CCH                                                                           Allyl   1-Ethylpiperazine                                                                        H                                         I-52    CH.sub.2 CCH                                                                           Allyl   2-Methylpiperazine                                                                       H                                         I-53    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Methyl  Piperazine H                                         I-54    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Methyl  N-Methylpiperazine                                                                       H                                         I-55    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Methyl  1-Ethylpiperazine                                                                        H                                         I-56    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Methyl  2-Methylpiperazine                                                                       H                                         I-57    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Cyclopropyl                                                                           Piperazine H                                         I-58    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Cyclopropyl                                                                           N-Methylpiperazine                                                                       H                                         I-59    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Cyclopropyl                                                                           1-Ethylpiperazine                                                                        H                                         I-60    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Cyclopropyl                                                                           2-Methylpiperazine                                                                       H                                         I-61    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Ethyl   1-Ethylpiperazine                                                                        H                                         I-62    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Ethyl   2-Methylpiperazine                                                                       H                                         I-63    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Allyl   1-Ethylpiperazine                                                                        H                                         I-64    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Allyl   2-Methylpiperazine                                                                       H                                         I-65    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Methyl  Imidazole  H                                         I-66    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Methyl  4-Methylimidazole                                                                        H                                         I-67    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Cyclopropyl                                                                           Imidazole  H                                         I-68    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Cyclopropyl                                                                           4-Methylimidazole                                                                        H                                         I-69    CH.sub.3 Cyclopropyl                                                                           1-Ethylpiperazine                                                                        CO.sub.2 H                                I-70    CH.sub.3 Cyclopropyl                                                                           2-Methylpiperazine                                                                       CO.sub.2 H                                I-71    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Cyclopropyl                                                                           1-Ethylpiperazine                                                                        CO.sub.2 H                                I-72    C(CH.sub.3).sub.2 CO.sub.2 H                                                           Cyclopropyl                                                                           2-Methylpiperazine                                                                       CO.sub.2 H                                __________________________________________________________________________

The present invention is described in detail by the followingPreparations and Examples:

Preparation 1

Preparation of 1-methyl-6,7-difluoro-1,4-dihydro-4-thioquinoline

A. Preparation of 1-methyl-6,7-difluro-1,2,3,4-tetrahydro-4-oxoquinoline

1-Methyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline carboxylic acid(7 g)was added to methyl alcohol(800 ml), and stirred at 0° C. After sodiumborohydride(4.3 g) and p-toluene sulfonic acid(cat.amount) were addedthereto, the reaction mixture was refuluxed for an hour, and the organicsolvent was removed under reduced pressure. To the residue was addedchloroform(500 ml), and it was washed twice with water (200 ml). Theseparated organic layer was dehydrated, and concentrated. The residuewas solidified with pet. ether, and dried to give thebright-yellow-above-indicated compound(3.6 g).

m.p.: 65°-67.5° C.

Yield: 77%

NMR: δ(CDCl₃) 2.65(t,2H), 2.90(s,3H), 3.40(t,2H), 6.40(dd,1H),7.78(m,1H)

B. Preparation of 1-methyl-6.7-difluoro-1,4-dihydro-4-oxoquinoline

1-Methyl-6,7-difluoro-1,2,3,4-tetrahydro-4-oxoquinoline(3.19 g) wasadded to 1,4-dioxane(90 ml). After p-chloranil(7.5 g) was added thereto,the reaction mixture was stirred at 80° C. After 24 hours, the organicsolvent was removed under reduced pressure. To the residue was addedchloroform(100 ml), and it was washed with 1N-sodium hydroxide solutionand water. The separated organic layer was dehydrated, and concentrated.The residue was solidified with pentane, and dried to give the whiteabove-indicated compound(1.6 g).

m.p.: 173.5°-175.5° C.

Yield: 52%

NMR: δ(CDCl₃) 3.75(s,3H), 6.20(d,1H), 7.20(ad,1H), 7.50(d,1H),8.20(dd,1H)

C.Preparation of 1-methyl-6,7-difluoro-1,4-dihydro-4-thioquinoline

1-Methyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline(1.6 g), phosphoruspentasulfide (5.3 g), and sodium bicarbonate(4.0 g) were added toacetonitrile(50 ml), and stirred at 60° C. for 4 hours, cooled to roomtemperature. The precipitates were filtered, and dried to give theyellow above-indicated compound(1.36 g).

m.p.: 198°-200° C.

Yield: 77%

NMR: δ(CDCl₃) 3.90(s,3H), 7,30(d,1H), 7.55-7.85(m,2H), 8.50-8.85(dd,1H)

Preparation 2

Preparation of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-thioquinoline

A. Preparation of1-cyclopropyl-6,7-difluoro-1,2,3,4-tetrahydro-4-oxoquinoline

1-Cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline carboxylic acid(20g) and sodium borohydride(11.5 g) were reacted in the same method asdescribed in Preparation 1-A to give the yellow above-indicatedcompound(12 g).

m.p.: 77.8°-80.4° C.

Yield: 86%

NMR: δ(CDCl₃) 0.65-1.05(m,4H), 2.20-2.40(m,1H), 2.60(t,2H), 3.50(t,2H),7.05(dd,1H), 7.70(dd,1H)

B. Preparation of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline

1-Cyclopropyl-6,7-difluoro-1,2,3,4-tetrahydro-4-oxoquinoline(10 g) andp-chloranil (22 g) were reacted in the same method as described inPreparation 1-B to give the white above-indicated compound(8.6 g).

m.p.: 169.6°-172° C.

Yield: 87%

NMR: δ(CDCl₃) 0.95-1.40(m,4H), 3.20-3.45(m,1H), 6.15(d,1H),7.50-7.80(m,2H), 8.10(dd,1H)

C. Preparation of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-thioquinoline

1-Cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline(4.8 g) andphosphorus pentasulfide(14.6 g) were reacted in the same method asdescribed in preparation 1-C to give the yellow above-indicatedcompound(4.98).

m.p.: 178°-177° C.

Yield: 94%

NMR: δ(CDCl₃) 0.90-1.45(m,4H), 3.25-3.60(m,1H), 7.20-7.50(m,2),7.60-7.92(dd,1H), 8.55-8.85(dd,1H)

Preparation 3:

Preparation of 1-ethyl,-6,7-difluoro-1,4-dihydro-4-thioquinoline

A. Preparation of 1-ethyl-6,7-difluoro-1,2,3,4-tetrahydro-4-oxoquinoline

1-Ethyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline carboxylic acid(20 g)and sodium borohydride(12 g) were reacted in the same method asdescribed in Preparation 1-A to give the bright-yellow above-indicatedcompound(11 g).

m.p.: 82°-84° C.

Yield: 80%

NMR: δ(CDCl₃) 1.15(t,3H), 2.70(t,2H), 3.40(q,2H), 3.50(t,2H),6.50(dd,1H), 7.65(dd,1H)

B. Preparation of 1-ethyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline

1-Ethyl-6,7-difluoro-1,2,3,4-tetrahydro-5-oxoquinoline(10 g) andp-chloranil (23 g) were reacted in the same method as described inPreparation 1-B to give the white above-indicated compound(6.7 g).

m.p.: 176°-178° C.

Yield: 68%

NMR: δ(CDCl₃) 1.20(t,3H), 4.10(q,2H), 6.20(d,1H), 7.70-8.05(m,2H),8.20(dd,1H)

C. Preparation of ethyl-6,7-difluoro-1,4-dihydro-4-thioquinoline

1-Ethyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline(6.7 g) and phosphoruspentasulfide(21 g) were reacted in the same method as described inPreparation 1-C to give the yellow above-indicated compound(4.4 g).

m.p.: 174°-176° C.

Yield: 60%

NMR: δ(CDCl₃) 1.40(t,3H), 4.40(q,2H), 7.30(d,1H), 7.95(d,1H),8.15(dd,1H), 8.65(dd,1H)

Preparation 4:

Preparation of 1-allyl-6,7-difluoro-1,4-dihydro-4-thioquinoline

A. Preparation of 1-allyl-6,7-difluoro-1,2,3,4-tetrahydro-4-oxoquinoline

1-Allyl-6,7-difluoro-1,4-dihydro-4-oxoquiniline carboxylic acid(25 g)and sodium borohydride(14.2 g) were reacted in the same method asdescribed in Preparsation 1-A to give the bright-yellow above-indicatedcompound(14 g).

m.p.: 57°-59° C.

Yield: 80%

NMR: δ(CDCl₃) 2.70(t,2H), 3.55(t,2H), 3.95(d,2H), 5.25(dd,2H),5.75-5.90(m,1H), 6.50(dd,1H), 7.65(dd,1H),

B. Preparation of 1-allyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline

1-Allyl-6,7-difluoro-1,2,3,4-tetrahydro-4-oxoquinoline(13.3 g) andp-chloranil (29.3 g) were reacted in the same method as described inPreparation 1-B to give the white above-indicated compound(12.3 g).

m.p.: 172°-174° C.

Yield: 93%

NMR: δ(CDCl₃) 4.70(d,2H), 5.18(d,1H), 5.38(d,1H), 5.95-6.10(m,1H),6.28(d,1H), 7.25(dd,1H), 7.55(d,1H), 8.25(dd,1H)

C. Preparation of 1-allyl-6,7-difluoro-1,4-dihydro-4-thioquinoline

1-Allyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline(12 g) and phosphoruspentasulfide(36 g) were reacted in the same method as described inPreparation 1-C to give the yellow above-indicated compound(10 g).

m.p.: 160°-163° C. (dec.)

Yield: 77%

NMR: δ(CDCl₃) 5.05(d,2H), 5.15(d,1H), 5.25(d,1H), 5,98-6.10(m,1H),7.35(d,1H), 7.95-8.05(m,2H), 8.65(dd,1H)

Preparation 5:

Preparation of1-methyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline

1-Methyl-6,7-difluoro-1,4-dihydro-4-thioquinoline(1.2 g) and piperazine(1.4 g) were added to pyridine(7 ml), and stirred at 130° C. for anhour. The organic solvent was removed under reduced pressure. To theresidue was added chloroform(50 ml), and it was washed with water. Theseparated organic layer was dehydrated, and concentrated. The residuewas solidified with water, and dried to give the yellow above-indicatedcompound(0.9 g).

m.p.: 255° C.

Yield: 54%

NMR: δ(DMSO-d₆) 2.60-3.10(m,8H), 3.90(s,3H), 7.10-7.65(m,3H), 8.40(d,1H)

Preparation 6:

Preparation of1-methyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Methyl-6,7-difluoro-1,4-thioquinoline(1.2 g) andN-methylpiperazine(1.9 ml) were reacted in the same method as describedin Preparation 5 to give the yellow above-indicated compound(1.1 g).

m.p.: 226°-228° C.(dec.)

Yield: 63%

NMR: δ(DMSO-d₆) 2.38(s,3H), 2.60(t,4H), 3.30(t,4H), 3.75(s,3H),6.58(d,1H), 7.05(m,2H), 8.40(d,1H)

Preparation 7:

Preparation of1-methyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Methyl-6,7-difluoro-1,4-thioquinoline(6 g) and 1-ethylpiparazine(9.5g) were reacted in the same method as described in Preparation 5 to givethe yellow above-indicated compound(4.2 g).

m.p.: 214°-216° C.(dec.)

Yield: 54%

NMR: δ(DMSO-d₆) 1.15(t,3H), 2.30-2.80(m,6H), 3.30(t,4H), 3.80(s,3H),6.60(d,1H), 7.05-7.25(m,2H), 8.50(d,1H)

Preparation 8:

Preparation of1-methyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Methyl-6,7-difluoro-1,4-thioquinoline(4.9 g) and2-methylpiperazine(6.8 g) were reacted in the same method as describedin Preparation 5 to give the yellow above-indicated compound(4.0 g).

m.p.: 177°-179° C.

Yield: 56%

NMR: δ(DMSO-d₆) 1.70(s,3H), 2.70-3.30(m,3H), 3.40-3.70(m,4H),3.90(s,3H), 6.65(d,1H), 7.05-7.30(m,2H), 8.50(d,1H)

Preparation 9:

Preparation of1-methyl-6-fluoro-7-imidazolyl-1,4-dihydro-4-thioquinoline

1-Methyl-6,7-difluoro-1,4-thioquinoline(2 g) and imidazole(1.9 g) wereadded to pyridine(20 ml), and stirred at 130° C. for 5 hours. Theorganic solvent was removed under reduced pressure. The residue wassolidified with water, and dried to give the yellow above-indicatedcompound(1.3 g).

m.p.: 255°-257° C.(dec.)

Yield: 51%

NMR: δ(DMSO-d₆) 3.90(s,3H), 7.15-7.25(m,2H),7.70-8.40(m,4H), 8.50(d,1H)

Preparation 10:

Preparation of1-methyl-6-fluoro-7-(4-methylimidazolyl)-1,4-dihydro-4-thioquinoline

1-Methyl-6,7-difluoro-1,4-thioquinoline(2 g) and 4-methylimidazole(2.3g) were reacted in the same method as described in Preparation 9 to givethe yellow above-indicated compound(1.4 g).

m.p.: 278°-280° C.(dec.)

Yield: 52%

NMR: δ(DMSO-d₆) 2.40(s,3H), 3.90(s,3H), 6.90-8.35(m,5H), 8.60(d,1H)

Preparation 11:

Preparation of1-cyclopropyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline

1-Cyclopropyl-6,7-difluoro-1,4-thioquinoline(1.5 g) and piperazine(1.64g) were reacted in the same method as described in Preparation 9 to givethe yellow above-indicated compound(1.1 g).

m.p.: 205°-208.3° C.

Yield: 55%

NMR: δ(DMSO-d₆) 0.90-1.40(m,4H), 2.65-3.60(m,9H), 7.05-7.70(m,3H),8.40(d,1H)

Preparation 12:

Preparation of1-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Cyclopropyl-6,7-difluoro-1,4-thioquinoline(1.5 g) andN-methylpiperazine (2.1 ml) were reacted in the same method as describedin Preparation 9 to give the yellow above-indicated compound(1.1 g).

m.p.: 181.5°-183.7° C.

Yield: 52%

NMR: δ(DMSO-d₆) 0.95-1.40(m,4H),2.38(s,3H), 2.62(t,4H), 3.30(t,4H).3.40-3.62(m,1H), 7.00-7.40(m,3H), 8.40(d,1H).

Preparation 13:

Preparation of1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Cyclopropyl-6,7-difluoro-1,4-thioquinoline (5 g) and 1-ethylpiperazine7.3 g) were reacted in the same method as described in Preparation 9 togive the yellow above-indicated compound(4.0 g).

m.p.: 178°-180° C.

Yield: 54%

NMR: δ(DMSO-d₆) 0.95-1.40(m,4H),2.30-2.75(m,6H), 3.30(t,4H),3.40-3.60(m,1H), 7.05-7.40(dd,3H), 8.45 (d,1H),

Preparation 14:

Preparation of1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Cyclopropyl6,7-difluoro-1,4-thioquinoline(5 g) and2-methylpiperazine(6.4 g) were reacted in the same method as describedin Preparation 9 to give the yellow above-indicated compound(4.8 g).

m.p.: 132°-132° C.(dec.)

Yield: 89%

NMR: δ(DMSO-d₆) 0.90-1.40(m,7H),2.40-3.75(m,8H), 7.10-7.38(dd,3H),8.50(d,1H)

Preparation 15:

Preparation of1-cyclopropyl-6-fluoro-7-imidazolyl-1,4-dihydro-4-thioquinoline

1-Cyclopropyl-6,7-difluoro-1,4-thioquinoline(5 g) and imidazole(4.3 g)were reacted in the same method as described in Preparation 9 to givethe yellow above-indicated compound(2.8 g).

m.p.: 205°-207° C.(dec.)

Yield: 45%

NMR: δ(DMSO-d₆) 1.10-1.20(m,2H), 1.28-1.38(m,2H), 3.65-3.85(m,1H),7.25(dd,2H), 7.80(s,1H), 7.95(dd,1H), 8.25(dd1H), 8.35(d,1H), 8.55(d,1H)

Preparation 16:

Preparation of1-cyclopropyl-6-fluoro-7-(4-methylimidazolyl)-1,4-dihydro-4-thioquinoline

1-Cyclopropyl-6,7-difluoro-1,4-thioquinoline(2.5 g) and4-methylpiperazine(2.6 g) were reacted in the same method as describedin Preparation 9 to give the yellow above-indicated compound(1.9 g).

m.p.: 242°-244° C.(dec.)

Yield: 58%

NMR: δ(DMSO-d₆) 1.00-1.35(m,4H), 2.45(s,3H), 3.72-3.85(m,1H),6.90(s,1H), 7.25-8.35(m,4H), 8.60(d,1H)

Preparation 17:

Preparation of1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline-3-carboxylicacid

1-Cyclopropyl-6,7-difluoro-1,4-thioquinoline-3-carboxylic acide(1.8 g)and 1-ethylpiperazine(2.2 g) were reacted in the same method asdescribed in Preparation 9 to give the yellow above-indicatedcompound(1.5 g).

m.p.: 232°-234° C.(dec.)

Yield: 60%

NMR: δ(DMSO-d₆) 1.20(t,3H), 1.40(m,2H), 2.75-3.40(m,6H), 3.60(m,4H),7.40(d,1H), 8.40(d,1H), 8.85(s,1H)

Preparation 18:

Preparation of1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline-3-carboxylicacid

1-Cyclopropyl-6,7-difluoro-1,4-thioquinoline-3-carboxylic acid(2 g) and2-methylpiperazine(2.2 g) were reacted in the same method as describedin Preparation 9 to give the yellow above-indicated compound(1.3 g).

m.p.: 240°-242° C.(dec.)

Yield: 45%

NMR: δ(DMSO-d₆) 1.20-1.45(m,4H), 1.70(s,3H), 2.75-3.30(m,4H),3.45-3.75(m,4H), 7.40(d,1H), 8.45(d,1H), 8.80(s,1H)

Preparation 19:

Preparation of1-ethyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline

1-Ethyl-6,7-difluoro-1,4-thioquinoline(1 g) and piperazine(1.15 g) werereacted in the same method as described in Preparation 9 to give theyellow above-indicated compound(1.2 g).

m.p.: 106°-108° C.

Yield: 89%

NMR: δ(DMSO-d₆) 1.40(t,3H), 2.60-3.45(m,8H), 4.40(q,2H),7.05-7.85(m,3H), 8.40(d,1H)

Preparation 20:

Preparation or1-ethyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Ethyl-6,7-difluoro-1,4-thioquinoline(1 g) and N-methylpiperazine (1.33g) were reacted in the same method as described in Preparation 9 to givethe yellow above-indicated compound(1.1 g).

m.p.: 184°-186° C.(dec.)

Yield: 77%

NMR: δ(DMSO-d₆) 1.40(t,3H), 2.28(s,3H),2.48-2.55(m,4H), 3.25-3.35(m,4H),4.42(q,2H), 7.05(d,1H), 7.15(d,1H), 7.88(d,1H), 8.40(d,1H)

Preparation 21:

Preparation of1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Ethyl-6,7-difluoro-1,4-thioquinoline(1 g) and 1-ethylpiperazine(1.52g) were reacted in the same method as described in Preparation 9 to givethe yellow above-indicated compound(1.23 g).

m.p.: 159°-161° C.

Yield: 82%

NMR: δ(DMSO-d₆) 1.20(t,3H), 1.40(t,3H), 2.40-3.50(m,8H), 3.80(q,2H),4.40(q,2H), 7.05-7.20(m,2H), 7.85(d,1H), 8.45(d,1H)

Preparation 22:

Preparation of1-ethyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Ethyl-6,7-difluoro-1,4-thioquinoline(1 g) and 2-methylpiperazine(1.33g) were reacted in the same method as described in Preparation 9 to givethe yellow above-indicated compound(1.25 g).

m.p.: 125°-127° C.(dec.)

Yield: 87%

NMR: δ(DMSO-d₆) 1.15(d,3H), 1.40(t,3H), 2.40-3.60(m,7H), 4.40(q,2H),7.05-7.40(m,3H), 8.45(d,1H)

Preparation 23:

Preparation of1-allyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline

1-Allyl-6,7-difluoro-1,4-thioquinoline(2 g) and piperazine(2.2 g) werereacted in the same method as described in Preparation 9 to give theyellow above-indicated compound(2.3 g).

m.p.: 93°-95° C.

Yield: 86%

NMR: δ(DMSO-d₆) 2.64-3.40(m,8H), 5.10(d,2H), 5.15-6.20(m,3H),7.05-7.90(m,3H), 8.40(d,1H)

Preparation 24:

Preparation of1-allyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Allyl-6,7-difluoro-1,4-thioquinoline(2 g) and N-methylpiperazine(2.5g) were reacted in the same method as described in Preparation 9 to givethe yellow above-indicated compound(2.3 g).

m.p.: 145°-147° C.

Yield: 82%

NMR: δ(DMSO-d₆) 2.25(s,3H), 2.60-3.30(m,8H), 5.10(d,2H),5.30-6.05(m,3H), 7.10-7.80(m,3H), 8.40(d,1H)

Preparation 25:

Preparation of1-allyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Allyl-6,7-difluoro-1,4-thioquinoline(2 g) and 2-ethylpiperazine(2.9 g)were reacted in the same method as described in Preparation 9 to givethe yellow above-indicated compound(2.35 g).

m.p.: 118°-120° C.

Yield: 80%

NMR: δ(DMSO-d₆) 1.15(t,3H), 2.30-3.30(m,10H), 5.05(d,2H),5.20-6.20(m,3H), 7.05-7.80(m,3H), 8.40(d,1H)

Preparation 26:

Preparation of1-allyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline

1-Allyl-6,7-difluoro-1,4-thioquinoline(2 g) and 2-methylpiperazine(2.5g) were reacted in the same method as described in Preparation 9 to givethe yellow above-indicated compound(1.9 g).

m.p.: 162°-164° C.

Yield: 68%

NMR: δ(DMSO-d₆) 1.05(d,3H), 2.40-3.50(m,7H), 5.05(d,2H),5.20(d,1H),5.30(d,1H), 5.98-6.12(m,1H), 7.00(d,1H), 7.18(d,1H), 7.85(d,1H), 8.38(d,1H)

EXAMPLE 1 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamide]-3-(1-methyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

To a solution of3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylic acid(0.73 g) suspended in 1:1(V/V)mixture of acetonitrile/water(30 ml) were added1-methyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.5 g) andsodium iodide(2.4 g). The reaction mixture was heated to 60° C. for 5hours.

The organic solvent was removed under reduced pressure. The residue wasadded acetone. The precipitates were filtered, and dried to give theabove-indicated compound(0.6 g).

IR: (KBr, cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 3.00-3.70(m,10H), 3.85(s,3H), 3.90(s,3H), 4.30(s,2H),5.05(d,1H), 5.65(dd,1H), 6.75(s,1H), 6.90-7.50(m,4H), 7.75(d,1H),8.30(d,1H), 9.20-9.60(m,1H)

EXAMPLE 2 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.7 g) and1-methyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.61 g).

IR: (KBr, cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 2.38(s,3H), 3.20-3.70(m,10H), 3.80(s,3H), 3.90(s,3H),4.25(s,2H), 4.95(d,1H), 5.50(dd,1H),6.60(s,1H),6.80-7.40(m,4H),7.70(d,1H), 8.70(d,1H), 9.40-9.65(m,1H)

EXAMPLE 3 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.67 g) and1-methyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.53 g).

IR: (KBr, cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.00(t,3H), 2.40(q,2H), 2.80-3.70(m,10H), 3.80(s,3H),3.95(s,3H), 4.30(s,2H), 4.95(d,1H), 5.50(dd,1H), 6.65(s,1H),6.80-7.30(m,4H), 7.90(d,1H), 8.40(d,1H), 9.30(d,1H)

EXAMPLE 4 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-(1-methyl-6-fluoro-7-(2-methyl)piperazinylquinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.7 g) and1-methyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.57 g).

IR: (KBr, cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-₆) 1.70(s,3H), 2.75-3.70(m,9H), 3.70(s,3H), 3.85(s,3H),4.40(s,2H), 5.00(d,1H), 5.50(dd,1H), 6.60(s,1H), 6.90-7.30(m,4H),7.80(d,1H), 9.40(d,1H)

EXAMPLE 5 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-(1-cyclopropyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.68 g) and1-cyclopropyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.5 g)were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.53 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 0.95-1.40(m,4H), 2.95-3.60(m,1H), 3.85(s,3H),4.20(s.e.,2H), 4.95(d,1H), 5.50(dd,1H), 6.60-7.30(m,5H), 7.70(d,1H),8.20(d,1H), 9.30-9.50(m,1H),

EXAMPLE 6 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.65 g) and 1-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.5 g) were reacted in the same manner asdescribed in Example 1 to give the above-indicated compound(0.52 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.00-1.45(m,4H), 2.30(s,3H), 3.10-3.80(m,11H),3.90(s,3H), 4.00-4.40(s.e.,2H), 4.95(d,1H), 5.50(dd,1H), 6.70(s,1H),6.95-7.30(m,4H), 7.70(d,1H), 8.45(d,1H), 9.42(d,1H)

EXAMPLE 7 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-3-[1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]-thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.63 g) and1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.57 g).

IR: (KBr, cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.00-1.40(m,7H), 2.45(q,2H), 3.00-3.80(m,11H),3.90(s,3H), 4.40(s,2H), 4.95(d,1H), 5.45(dd,1H), 6.65(s,1H),6.90-7.35(m,4H), 7.70(d,1H), 8.45(s,1H), 9.40 (d,1H)

EXAMPLE 8 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.65 g) and1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.61 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.00-1.35(m,4H), 1.74(s,3H), 2.70-3.75(m,10H),3.90(s,3H), 4.40(s,2H), 5.00(d,1H), 5.50(dd,1H), 6.65(s,1H),6.90-7.30(m,4H), 7.70(d,1H), 8.40(d,1H), 9.40(d,1H)

EXAMPLE 9 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-(1-ethyl-6-fluoro-7-piperazinylquinolinum-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-ethyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoine(0.21 g) werereacted in the same manner as described in Example 1 to give theabove-indicated compound(0.24 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.45(t,3H), 2.65-3.60(m,10H), 3.90(s,3H), 4.10(q,2H),4.40(s,2H), 5.00(d,1H), 5.50(dd,1H), 6.60(s,1H), 6.85-7.20(m,4H),7.75(d,1H), 8.40(d,1H), 9.45 (d,1H)

EXAMPLE 10 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-(1-ethyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-ethyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.25 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.40(t,3H), 2.45(s,3H), 2.65(t,4H), 3.30-3.60(m,6H),3.90(s,3H), 4.10(q,2H), 4.40(s,2H), 5.05(d,1H), 5.50(dd,1H), 6.65(s,1H),7.05-7.40(m,4H), 7.45(d,1H), 8.45(d,1H), 9.40(d,1H)

EXAMPLE 11 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylat

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.23g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.26 g).

IR: (KBr,cm⁻¹) 1760(β-lactam).

NMR: δ(DMSO-d₆) 1.20(t,3H), 1.40(t,3H), 2.30-2.85(m,6H), 3.30-3.85(m,6H), 3.85(s,3H), 4.10(q,2H), 4.40(s,2H), 4.95(d,1H), 5.50(dd,1H),6.65(s,1H), 6.80-7.15(m,4H), 7.25(d,1H), 8.45(d,1H), 9.40(d,1H)

EXAMPLE 12 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-ethyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.26 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.40(t,3H), 1.70(s,3H), 2.65-3.25(m,3H),3.45-3.75(m,6H), 3.90(s,3H), 4.10(q,2H), 4.45(s,2H), 5.00(d,1H),5.50(dd,1H), 6.65(s,1H), 6.70-7.30(m,4H), 7.40(d,1H), 8.45(d,1H),9.40(d,1H)

EXAMPLE 13 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-(1-allyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-allyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.2 g) werereacted in the same manner as described in Example 1 to give theabove-indicated compound(0.23 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 2.65-3.60 (m,10H), 3.90(s,3H), 4.40-4.50(m,4H),4.95(d,1H), 5.20(d,2H), 5.45(dd,1H), 6.10-6.25(m,1H), 6.65 (s,1H),6.90-7.45(m,4H), 7.75(d,1H), 8.40(d,1H), 9.40(d,1H)

EXAMPLE 14 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and 1-allyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.2 g) were reacted in the same manner asdescribed in Example 1 to give the above-indicated compound(0.25 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 2.40(s,3H), 2.65-3.60(m,10H), 3.90(s,3H),4.40-4.50(m,4H), 7.55(d,1H), 8.40(d,1H), 9.45(d,1H)

EXAMPLE 15 Synthesis of7-[(Z)-2(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-allyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.24 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.20(t,3H), 2.35-2.70(m,6H), 3.30-3.65(m,6H).3.95(s,3H), 4.35-4.50(m,4H), 4.95-5.05(m,3H), 5.45(dd,1H),5.95-6.05(m,1H), 6.65(s,1H), 6.70-7.25(m,4H), 7.30(d,1H), 8.40(d,1H),9.40(d,1H)

EXAMPLE 16 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3g) and1-allyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.2g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.26 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.70(s,3H), 2.70-3.20(m,3H), 3.45-3.70(m,6H), 3.90(s,3H)4.40-4.50(m,4H), 5.00(d,1H), 5.10(d,2H), 5.45(dd,1H), 6.00-6.10(m,1H),6.65(s,1H), 6.70-7.30(s,4H), 7.35(d,1H), 8.50(d,1H), 9.40(d,1H)

Example 17 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-(1-methyl-6-fluoro-7-imidazolylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

To a solution of3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) suspended in 1:1(V/V) mixture of acetonitrile/water(40 ml)were added1-methyl-6-fluoro-7-imidazolyl-1,4-dihydro-4-thioquinoine(0.51 g) andsodium iodide(2.6 g). The reaction mixture was heated to 60° C. for 5hours. The organic solvent was removed under reduced pressure. Theresidue was added acetone. The precipitates were filtered, andchromatographed over silica gel. Elution with a 4:1(V/V) mixture ofacetonitrile/water gave the above-indicated compound(0.65 g).

IR: (KBr,cm⁻¹) 1761(β-lactam)

NMR: δ(DMSO-d₆) 3.55(s,2H), 3.85(s,3H), 3.95(s,3H), 4.40(s,2H),4.95(d,1H), 5.50(dd,1H), 6.65(s,1H), 6.70(d,1H), 6.80-7.40(m,6H),7.85(s,1H), 8.50(d,1H), 9.40(d,1H)

EXAMPLE 18 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(4-methylimidazolyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.45 g) and1-methyl-6-fluoro-7-(4-methylimidazolyl)-1,4-dihydro-4-thioquinoline(0.3g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.38 g).

IR: (KBr,cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 2.40(s,3H), 3.50(s,2H), 3.80(s,3H), 3.90(s,3H)4.40(s,2H), 5.00(d,1H), 5.50(dd,1H), 6.60-6.85(m,3H), 7.05-7.60(m,5H),8.50(d,1H), 9.40(d,1H)

EXAMPLE 19 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamide]-3-(1-cyclopropyl-6-fluoro-7-imidazolylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamide]-3-cephem-4-carboxylicacid(0.8 g) and1-cyclopropyl-6-fluoro-7-imidazolyl-1,4-dihydro-4-thioquinoline(0.55 g)were reacted in the same manner as described in Example 17 to give theabove-indicated compound(0.66 g).

IR: (KBr,cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 0.95-1.40(m,4H), 3.40-3.65(m,3H), 3.90(s,3H),4.40(s,2H), 4.95(d,1H), 5.50(dd,1H), 6.65(s,1H), 6.85-7.35(m,6H)7.40(d,1H), 7.85(s,1H), 8.50(d,1H), 9.40(d,1H)

EXAMPLE 20 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(4-methylimidazolyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) and 1-cyclopropyl-6-fluoro-7-(4-methylimidazolyl)-1,4-dihydro-4-thioquinoline(0.58 g) were reacted in the same manner asdescribed in Example 17 to give the above-indicated compound(0.67 g).

IR: (KBr,cm⁻¹) 1761(β-lactam)

NMR: δ(DMSO-d₆) 0.90-1.40(m,4H), 2.45(s,3H), 3.45-3.60(m,3H),3.90(s,3H), 4.40(s,2H), 5.00(d,1H), 5.50(dd,1H), 6.65(s,1H),6.90-7.50(m,6H), 7.65(s,1H), 8.45(d,1H), 9.40(d,1H)

EXAMPLE 21 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-(1-methyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.26 g) werereacted in the same manner as described in Example 1 to give theabove-indicated compound(0.34 g).

IR: (KBr,cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 2.65-3.10(m,8H), 3.58(s,2H), 3.90(s,3H), 4.40(s,2H),5.05-5.80(m,4H), 5.85-6.15(m,3H), 6.85(s,1H), 6.95-7.30(m,4H),7.65(d,1H), 8.40(d,1H), 9.40(d,1H),

EXAMPLE 22 Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.27g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.33 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 2.40(s,3H), 2.60-3.65(m,10H), 3.80(s,3H), 4.40(s,2H),5.00-6.10(m,7H), 6.55-7.05(m,4H), 8.40(d,1H), 9.45(d,1H)

EXAMPLE 23 Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.28g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.33 g).

IR: (KBr,cm⁻¹) 1761(β-lactam)

NMR: δ(DMSO-d₆) 1.20(t,3H), 2.35-2.80(m,6H), 3.30-3.60(m,6H),3.80(s,3H), 4.45(s,2H), 5.05-5.90(m,6H), 6.10-6.70(m,3H), 7.05-7.25(m,2H), 8.50(d,1H), 9.45(d,1H),

EXAMPLE 24 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.27g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.34 g).

IR: (KBr,cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 1.70(s,3H), 2.70-3.75(m,9H), 3.85(s,3H), 4.45(s,2H),5.00-5.80(m,6H), 5.95-6.65(m,3H), 7.05-7.30(m,2H), 8.50(d,1H),9.40(d,1H)

EXAMPLE 25 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-(1-cyclopropyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-cyclopropyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.2 g)were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.25 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 0.85-1.40(m,4H), 2.80-3.90(m,11H), 4.30-4.80(m,4H),4.90-5.30(m,3H), 6.90-7.56(m,5H), 7.70(d,1H), 8.20(d,1H),9.20-9.50(m,1H)

EXAMPLE 26 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.34 g).

IR: (KBr,cm⁻¹) 1761(β-lactam)

NMR: δ(DMSO-d₆) 0.95-1.40(m,4H), 2.35(s,3H), 3.00-3.70(m,11H),4.42-4.80(m,3H), 5.00-5.40(m,3H), 5.70-6.00(m,3H),6.00(s,1H),6.95-7.40(m,4H),7.70(d,1H), 8.20(d,1H), 9.40(d,1H)

EXAMPLE 27 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.23g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.24 g).

IR: (KBr,cm⁻¹) 1761(β-lactam)

NMR: δ(DMSO-d₆) 0.90-1.40(m,7H), 2.45-3.55(m,13H), 4.42-4.90(m,3H),5.05-5.50(m,3H), 5.65-6.10(m,3H),8.50(s,1H), 6.90-7.30(m,4H) 7.45(d,1H),8.45(d,1H), 9.45(d,1H)

EXAMPLE 28 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)-4-dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.23 g).

IR: (KBr,cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 1.00-1.40(m,4H), 1.70(s,3H),2.90-3.75(m,19H),4.45-4.95(m,3H), 5.00-5.45(m,3H), 5.70-6.15(m,3H), 6.60(s,1H),6.80-7.25(m,4H), 7.40(d,1H), 8.50(d,1H), 9.45(d,1H)

EXAMPLE 29 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-(1-ethyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.15 g) and1-ethyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.1 g) werereacted in the same manner as described in Example 1 to give theabove-indicated compound(0.11 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.45(t,3H), 2.65-3.55(m,10H), 4.10 (q,2H),4.45-5.40(m,6H), 5.75-6.20(m,3H), 6.60(s,1H), 6.90-7.55 (m,4H),7.70(d,1H), 8.40(d,1H), 9.40(d,1H),

EXAMPLE 30 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.15 g) and1-ethyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.1g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.11 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.40(t,3H), 2.40(s,3H), 2.60-3.60(m,10H), 4.10(q,2H),4.40-5.55(m,6H), 5.80-6.25(m,3H), 6.65(s,1H), 6.90-7.35(m,4H),7.40(d,1H), 8.45(d,1H), 9.45(d,1H),

EXAMPLE 31 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.15 g) and1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.11g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.12 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.20(t,3H), 1.40(t,3H), 2.50-3.55(m,12H), 4.10(q,2H),4.40-4.85(m,3H), 4.95-5.50(m,3H), 5.80-6.15(m,3H),6.60(s,1H),6.75-7.20(m,4H), 7.30(d,1H), 8.45(d,1H), 9.40(d,1H)

EXAMPLE 32 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.15 g) and1-ethyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.1g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.12 g).

IR: (KBr,cm⁻¹) 1761(β-lactam)

NMR: δ(DMSO-d₆) 1.40(t,3H), 1.70(s,3H), 2.65-3.70(m,9H), 4.10(q,2H),4.45-4.90(m,3H), 5.00-5.65(m,3H), 5.90-6.20(m,3H), 6.60-6.70(m,2H),6.90-7.25(m,3H), 7.40(d,1H), 8.45(d,1H), 9.40(d,1H)

EXAMPLE 33 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-(1-allyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.15 g) and1-allyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.1 g) werereacted in the same manner as described in Example 1 to give theabove-indicated compound(0.12 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 2.65-3.65(m,10H), 4.40-4.50(m,4H), 4.95-6.20(m,10H),6.65(s,1H), 6.90-7.50(m,4H), 7.75(d,1H), 8.40(d,1H), 9.45(d,1H)

EXAMPLE 34 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.15 g) and1-allyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.1g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.11 g).

IR: (KBr,cm⁻¹) 1758(β-lactam)

NMR: δ(DMSO-d₆) 2.40(s,3H), 2.70-3.55(m,10H), 4.45-4.55(m,4H),4.95-5.45(m,6H), 5.50-6.15(m,4H), 6.60(s,1H), 6.85-7.50(m,4H),7.55(d,1H), 8.40(d,1H), 9.40(d,1H)

EXAMPLE 35 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.15 g) and1-allyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.11g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.12 g).

IR: (KBr,cm⁻¹) 1759(β-lactam)

NMR: δ(DMSO-d₆) 1.15(t,3H), 2.40-3.50(m,12H),4.40(m,4H),4.95-5.60(m,6H), 5.75-6.15(m,4H), 6.60-6.70(m,2H), 6.90-7.15(m,3H),7.30(d,1H), 8.40(d,1H), 9.40(d,1H),

EXAMPLE 36 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.15 g) and1-allyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.1g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.11 g).

IR: (KBr,cm⁻¹) 1758(β-lactam)

NMR: δ(DMSO-d₆) 1.70(s,3H), 2.70-3.75 (m,9H), 4.45 (m,4H)4.80-5.45(m,6H), 5.70-6.15(m,4H), 6.65(m,2H), 6.85-7.30(m,3H),7.35(d,1H), 8.50(d,1H), 9.45(d,1H)

EXAMPLE 37 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-(1-methyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.26 g) werereacted in the same manner as described in Example 1 to give theabove-indicated compound(0.33 g).

IR: (KBr,cm⁻¹) 1759(β-lactam)

NMR: δ(DMSO-d₆) 2.60-3.50(m,9H), 3.65(s,2H), 3.90(s,3H), 4.45(s,2H),4.75(s,2H), 5.05(d,1H), 5.55(dd,1H), 6.65(s,1H), 6.80`7.50(m,4H),7.65(d,1H), 8.40(d,1H), 9.45(d,1H)

EXAMPLE 38 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.27g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.34 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.70(s,3H), 2.70-3.75 (m,9H), 4.45(m,4H),4.80-5.45(m,6H), 5.70-6.15(m,4H), 6.65 (m,2H), 6.85-7.30(m,3H),7.35(d,1H), 8.50(d,1H), 9.45(d,1H)

EXAMPLE 39 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]-thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]--3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.29g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.36 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.15(t,3H), 2.40-3.50(m,11H), 3.60(s,2H), 3.80(s,3H),4.40(s,2H), 4.80(s,2H), 5.05(d,1H), 5.50(dd,1H), 6.60(m,2H),6.75-7.20(m,3H), 7.25(d,1H), 8.50(d,1H), 9.45(d,1H)

EXAMPLE 40 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.27g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.35 g).

IR: (KBr,cm⁻¹) 1759(β-lactam)

NMR: (DMSO-d₆) 1.70(s,3H), 2.70-3.70(m,10H), 3.85(s,3H), 4.45(s,2H),4.80(s,2H), 5.00(d,1H), 5.50(dd,1H), 6.65(m,2H), 6.85-7.20(m,3H),7.30(d,1H), 8.50(d,1H), 9.45(d,1H)

EXAMPLE 41 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-(1-cyclopropyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-cyclopropyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.28 g)were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.33 g).

IR: (KBr,cm⁻¹) 1758(β-lactam)

NMR: δ(DMSO-d₆) 0.90-1.40(m,4H), 2.60-3.40(m,10H), 3.60(s,2H),4.45(s,2H), 4.75(s,2H), 5.05(d,1H), 5.55(dd,1H), 6.60(s,1H),6.80-7.40(m,4H), 7.70(d,1H), 8.40(d,1H), 9.45(d,1H)

EXAMPLE 42 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.29g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.32 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 0.95-1.40(m,4H), 2.35(s,3H), 2.65-3.60(m,12H),4.40(s,2H), 4.70(s,2H), 4.95(d,1H), 5.50(dd,1H), 6.65 (s,1H),6.85-7.30(m,4H), 7.40(d,1H), 8.40(d,1H), 9.40(d,1H)

EXAMPLE 43 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z) -2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylic acid(0.4 g) and1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.3g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.32 g).

IR: (KBr,cm⁻¹) 1759(β-lactam)

NMR: δ(DMSO-d₆) 0.90-1.40(m,7H), 2.30-3.60(m,14H), 4.45(s,2H),4.70(s,2H), 4.95 (d,1H), 5.55(dd,1H), 6.60(s,1H), 6.90-7.35(m,4H),7.40(d,1H), 8.45(d,1H), 9.40(d,1H)

EXAMPLE 44 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.29g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.33 g).

IR: (KBr,cm⁻¹) 1759(β-lactam)

NMR: δ(DMSO-d₆) 0.95-1.40(m,4H), 1.70(s,3H), 2.70-3.75(m,11H),4.40(s,2H), 4.75(s,2H), 5.05(d,1H), 5.45(dd,1H), 6.65(s,1H),6.85-7.30(m,4H), 7.40(d,1H), 8.50(d,1H), 9.45(d,1H)

EXAMPLE 45 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-(1-ethyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.5 g) and1-ethyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.33 g) werereacted in the same manner as described in Example 1 to give theabove-indicated compound(0.40 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.40(t,3H), 2.60-3.50(m,11H), 4.10-4.70(m,6H),5.00(d,1H), 5.50(dd,1H), 6.65(s,1H), 6.90-7.50(m,4H), 7.70(d,1H),8.40(d,1H), 9.40(d,1H)

EXAMPLE 46 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.5 g) and1-ethyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.35g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.39 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.40(t,3H), 2.40(s,3H), 2.65-3.55(m,11H),4.10-4.75(m,6H), 4.95(d,1H), 5.50(dd,1H), 6.65(s,1H), 6.85-7.30(m,4H),7.40(d,1H), 8.45(d,1H), 9.45(d,1H)

EXAMPLE 47 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.5 g) and1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.37g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.45 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.20(t,3H), 1.40(t,3H), 2.30-3.60(m,13H),4.10-4.40(m,4H), 4.80(s,2H), 5.00(d,1H), 5.45(dd,1H), 6.70(m,2H),6.85-7.20(m,3H), 7.25(d,1H), 8.45(d,1H), 9.45(d,1H)

EXAMPLE 48 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.5 g) and1-ethyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.35g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.40 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.40(t,3H), 1.70(s,3H), 2.65-3.70(m,10H),4.10-4.80(m,6H), 5.00(d,1H), 5.60(dd,1H), 6.65(m,2H), 6.85-7.30(m,3H),7.35(d,1H), 8.45(d,1H), 9.40(d,1H)

EXAMPLE 49 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-(1-allyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.5 g) and1-allyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.31 g) werereacted in the same manner as described in Example 1 to give theabove-indicated compound(0.41 g).

IR: (KBr,cm⁻¹) 1758(β-lactam)

NMR: δ(DMSO-d₆) 2.65-3.60(m,11H), 4.40-4.80(m,6H), 5.00-5.25(m,3H),5.65(dd,1H), 6.05-6.20(m,1H), 6.65(s,1H), 6.85-7.40(m,4H), 7.80(d,1H),8.40(d,1H), 9.45(d,1H)

EXAMPLE 50 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.5 g) and1-allyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.34g) were reacted in the same manner as described in Example. 1 to givethe above-indicated compound(0.42 g).

IR: (KBr,cm⁻¹) 1759(β-lactam)

NMR: δ(DMSO-d₆) 2.40(s,3H), 2.65-3.55(m,11H), 4.45-4.70(m,6H),5.00(m,3H), 5.60(dd,1H), 5.90-6.05(m,1H), 6.60(s,1H), 6.80-7.40(m,1H),7.55(d,1H), 8.40(d,1H), 9.45(d,1H)

EXAMPLE 51 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.5 g) and1-allyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.35g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.40 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.20(t,3H), 2.30-3.55(m,13H), 4.40-4.80(m,6H),4.95(m,3H), 5.60(dd,1H), 5.95-6.10(m,1H), 6.65(m,2H), 6.80-7.20(m,3H),7.30(d,1H), 8.40(d,1H), 9.45(d,1H)

EXAMPLE 52 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]-3-cephem-4-carboxylicacid(0.5 g) and1-allyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.34g) were reacted in the same manner as described in Example 1 to give theabove-indicated compound(0.38 g).

IR: (KBr,cm⁻¹) 1759(β-lactam)

NMR: δ(DMSO-d₆) 1.70(s,3H), 2.70-3.75(m,10H), 4.40-4.75(m,6H),5.00(d,1H), 5.10(d,2H). 5.55(dd,1H), 6.60(m,1H), 6.60(m,2H),6.80-7.25(m,3H), 7.40(d,1H), 8.50(d,1H), 9.45(d,1H)

EXAMPLE 53 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-(1-ethyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.24 g) werereacted in the same manner as described in Example 17 to give theabove-indicated compound(0.29 g).

IR: (KBr,cm⁻¹) 1763(β-lactam)

NMR: δ(DMSO-d₆) 1.45(d,6H), 2.60-3.55(m,10H), 3.90(s,3H), 4.40(s,2H),5.00(d,1H), 5.65(dd,1H), 6.70(s,1H), 7.00-7.40(m,4H), 7.65(d,1H),8.40(d,1H), 9.25(d,1H)

EXAMPLE 54 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.25g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.29 g).

IR: (KBr,cm⁻¹) 1763(β-lactam)

NMR: δ(DMSO-d₆) 1.38(s,3H), 1.42(s,3H), 2.30(s,3H), 2.70-3.60(m,10H),3.95(s,3H), 4.40(s,2H), 5.06(d,1H), 5.65(dd,1H), 6.70(s,1H), 7.05(d,1H),7.15(m,2H), 7.35(d,1H), 7.85(d,1H), 8.40(d,1H), 9.10(d,1H)

EXAMPLE 55 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.26g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.31 g).

IR: (KBr,cm⁻¹) 1761 (β-lactam)

NMR: δ(DMSO-d₆) 1.20(t,3H), 1.40(s,6H), 2.30-2.85(m,6H),3.20-3.55(m,6H), 3.95(s,3H), 4.40(s,2H), 5.10(d,1H), 5.65(dd,1H),6.70(s,1H), 6.80(d,1H), 6.90-7.30(m,3H), 7.35(d,1H), 8.50(d,1H),9.30(d,1H)

EXAMPLE 56 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.25g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.30 g).

IR: (KBr,cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 1.45(s,6H), 1.70(s,3H),2.70-3.70(m,9H), 3.90(s,3H),4.40(s,2H), 5.10(d,1H), 5.65(dd,1H), 6.70(m,2H), 6.80-7.20(m,3H),7.40(d,1H), 8.50(d,1H), 9.25(d,1H)

EXAMPLE 57 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-(1-cyclopropyl-6-fluoro-7-piperazinylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) and1-cyclopropyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-thioquinoline(0.54 g)were reacted in the same manner as described in Example 17 to give theabove-indicated compound(0.67 g).

IR: (KBr,cm⁻¹) 1763(β-lactam)

NMR: δ(DMSO-d₆) 0.90-1.45(m,10H), 2.70-3.55 (m,11H), 4.40(s,2H),5.05(d,1H), 5.65(dd,1H), 6.70(s,1H), 6.90-7.50(m,4H), 7.70(d,1H),8.40(d,1H), 9.30(d,1H)

EXAMPLE 58 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) and1-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.56g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.66 g).

IR: (KBr,cm⁻¹) 1763(β-lactam)

NMR: δ(DMSO-d₆) 0.95-1.50(m,10H), 2.40(s,3H), 2.60-3.55(m,11H),4.40(s,2H), 5.10(d,1H), 5.65(dd,1H), 6.70(s,1H), 6.85-7.30(m,4H),7.40(d,1H), 8.40(d,1H), 9.20(d,1H)

EXAMPLE 59 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) and1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.58g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.68 g).

IR: (KBr, cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 1.00-1.50(m,13H), 2.40-2.65(m,6H), 3.30-3.60(m,7H),4.25(s.e., 2H), 5.00(d,1H), 5.65(dd,1H), 6.70(s,1H), 7.10(d,1H),7.50(d,1H), 7.75(d,1H), 7.85(d,1H), 8.10(d,1H), 8.35(d,1H), 8.90(d,1H)

EXAMPLE 60 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) and1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.56g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.64 g).

IR: (KBr,cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 1.00-1.45(m,10H), 1.70(s,3H), 2.70-3.70(m,10H),4.25(s,2H), 5.00(d,1H), 5.60(dd,1H), 6.70(s,1H), 6.85-7.30(m,4H),7.50(d,1H), 8.50(d,1H), 9.20(d,1H)

EXAMPLE 61 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) and1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.53g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.67 g).

IR: (KBr,cm⁻¹) 1763(β-lactam)

NMR: δ(DMSO-d₆) 1.20(t,3H), 1.40(t,3H), 1.45(s,6H), 2.50-3.55(m,12H),4.10-4.45(m,4H), 5.00(d,1H), 5.65(dd,1H), 6.70(s,1H), 6.80-7.20(m,4H),7.40(d,1H), 8.45(d,1H), 9.20(d,1H)

EXAMPLE 62 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-ethyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl]-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) and1-ethyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.51g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.65 g).

IR: (KBr,cm⁻¹) 1762(β-lactam)

NMR: δ(DMSO-d₆) 1.40(t,3H), 1.45(s,6H), 1.70(s,3H), 2.65-3.50(m,9H)4.15-4.35(m,4H), 5.00(d,1H), 5.65(dd,1H), 6.70(m,2H), 6.85-7.30(m,3H),7.50(d,1H), 8.45(d,1H), 9.30(d,1H)

EXAMPLE 63 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) and1-allyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.51g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.66 g).

IR: (KBr,cm⁻¹) 1763(β-lactam)

NMR: δ(DMSO-d₆) 1.20(t,3H), 1.40(s,6H), 2.50-3.50(m,12H),4.40-4.55(m,4H), 4.95-5.10(m,3H), 5.70-6.00(m,2H), 6.70(m,2H),6.80-7.30(m,3H), 7.55(d,1H), 8.40(d,1H), 9.25(d,1H)

EXAMPLE 64 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-allyl-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.8 g) and1-allyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline(0.49g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.63 g).

IR: (KBr,cm⁻¹) 1763(β-lactam)

NMR: δ(DMSO-d₆) 1.40(s,6H), 1.70(s,3H), 2.70-3.75(m,9H), 4.45(m,4H),5.00-5.10(m,3H), 5.65(dd,1H), 6.05(m,1), 6.65(m,2H), 6.90-7.30(m,3H),7.45(d,1H), 8.50(d,1H), 9.45(d,1H)

EXAMPLE 65 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-(1-ethyl-6-fluoro-7-imidazolylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-imidazolyl-1,4-dihydro-4-thioquinoline(0.22 g) werereacted in the same manner as described in Example 17 to give theabove-indicated compound(0.31 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.50(s,6H), 3.65(s,2H), 3.90(s,3H), 4.45(s,2H),5.00(d,1H), 5.65(dd,1H), 6.65(d,1H), 6.70(s,1H), 6.85-7.40(m,6H),7.85(s,1H), 8.50(d,1H), 9.40(d,1H)

EXAMPLE 66 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-methyl-6-fluoro-7-(4-methylimidazolyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-methyl-6-fluoro-7-(4-methylimidazolyl-1,4-dihydro-4-thioquinoline(0.23g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.33 g).

IR: (KBr,cm⁻¹) 1761(β-lactam)

NMR: δ(DMSO-d₆) 1.50(s,6H), 2.40(s,3H), 3.65(s,2H), 3.95(s,3H),4.45(s,2H), 5.05(d,1H), 5.70(dd,1H), 6.60-6.85(m,3H), 6.90-7.40(m,4H),7.60(d,1H), 8.50(d,1H), 9.30(d,1H)

EXAMPLE 67 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-(1-cyclopropyl-6-fluoro-7-imidazolylquinolinium-4-yl)thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-cyclopropyl-6-fluoro-7-imidazolyl-1,4-dihydro-4-thioquinoline(0.18 g)were reacted in the same manner as described in Example 17 to give theabove-indicated compound(0.24 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.00-1.45(m,10H), 3.50-3.65(m,3H), 4.45(s,2H),5.10(d,1H), 5.70(dd,1H), 6.70(s,1H), 6.90-7.40(m,7H), 7.85(s,1H),8.50(d,1H), 9.35(d,1H)

EXAMPLE 68 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-cyclopropyl-6-fluoro-7-(4-methylimidazolyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.3 g) and1-cyclopropyl-6-fluoro-7-(4-methylimidazolyl)-1,4-dihydro-4-thioquinoline(0.19g) were reacted in the same manner as described in Example 17 to givethe above-indicated compound(0.23 g).

IR: (KBr,cm⁻¹) 1761(β-lactam)

NMR: δ(DMSO-d₆) 0.95-1.45(m,10H), 2.45(s,3H), 3.45-3.60(m,3H),4.50(s,2H), 5.10(d,1H), 5.70 (dd,1H), 6.70 (s,1H), 6.90 (s,1H),6.95-7.60 (m,6H ), 8.45(d,1H), 9.30(d,1H)

EXAMPLE 69 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-cyclopropyl-3-carboxylicacid-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid (0.7 g) and1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline-3-carboxylicacid(0.63 g) were reacted in the same manner as described in Example 17to give the above-indicated compound(0.59 g).

IR: (KBr,cm⁻¹) 1761(β-lactam)

NMR: δ(DMSO-d₆) 1.00-1.40(m,7H), 2.75-3.70(m,13H), 3.90(s,3H),4.40(s,2H), 5.00(d,1H), 5.50(dd,1H), 6.65(s,1H), 7.40(d,1H), 8.40(d,1H),8.85(s,1H), 9.50(d,1H)

EXAMPLE 70 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[1-cyclopropyl-1-3-carboxylicacid-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylicacid(0.6 g) and1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline-3-carboxylicacid(0.52 g) were reacted in the same manner as described in Example 17to give the above-indicated compound(0.52 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.10-1.45(m,4H), 1.70(s,3H), 2.75-3.70(m,10H),3.90(s,3H), 4.40(s,2H), 5.05(d,1H), 5.50(dd,1H), 6.65(s,1H), 7.40(d,1H),8.45(d,1H), 8.75(s,1H), 9.50(d,1H)

EXAMPLE 71 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-cyclopropyl-3-carboxylicacid-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid (0.4 g) and1-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4-dihydro-4-thioquinoline-4-carboxylicacid(0.31 g) were reacted in the same manner as described in Example 17to give the above-indicated compound(0.34 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.00-1.50(m,13H), 2.75-3.60(m,13H), 4.50(s,2H),5.10(d,1H), 5.70(dd,1H), 6.70(s,1H), 6.95-7.40(m,3H), 8.40(d,1H),8.80(s,1H), 9.55(d,1H)

EXAMPLE 72 Synthesis of7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-[1-cyclopropyl-3-carboxylicacid-6-fluoro-7-(2-methylpiperazinyl)quinolinium-4-yl]thiomethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-cephem-4-carboxylicacid(0.4 g) and1-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)-1,4-dihydro-4-thioquinoline-3-carboxylicacid(0.3 g) were reacted in the same manner as described Example 17 togive the above-indicated compound(0.32 g).

IR: (KBr,cm⁻¹) 1760(β-lactam)

NMR: δ(DMSO-d₆) 1.10-1.45(m,10H), 1.70(s,3H),2.75-3.60(m,10H)4.50(s,2H), 5.10(d,1H), 5.70(dd,1H), 6.70(s,1H), 6.90-7.35(m,3H),8.50(d,1H), 8.85(s,1H), 9.50(d,1H)

In order to illustrate the usefulness of the invented compounds, theminimal inhibitory concentrations-(MIC) thereof against standard strainswere determined and compared with Cefotaxime, a known compound.

Also, the in vitro antibacterial activity was determined by a two-folddilution method as described below:

That is, the two-fold serial dilutions of the compound were made anddispersed in Muller Hinton Broth medium. Standard test strain which hadthe 10⁶ CFU per ml was inoculated on the medium, and was incubated at37° C. for 18 to 20 hours. The results of the MIC tests are shown inTable 3.

                                      TABLE 3                                     __________________________________________________________________________    Antibacterial Activity (MIC, μg/ml)                                        Strains                                                                             Bacillus                                                                            Staphylococcus                                                                       Staphylococcus                                                                       Streptococcus                                                                        Pseudomonas                                                                          Esherichia                                                                           Klebsiella                     Compound                                                                            subtilis                                                                            aureus epidermidis                                                                          faecalis                                                                             aeurginosa                                                                           coli   pneumoniae                     No.   ATCC 6633                                                                           ATCC 65389                                                                           ATCC 12228                                                                           ATCC 10541                                                                           NCTC 10490                                                                           ATCC 25922                                                                           ATCC 10031                     __________________________________________________________________________    I-1   0.2   0.2    0.1    0.05   1.56   0.78   0.2                            I-2   0.39  1.56   0.78   0.39   3.13   12.5   0.39                           I-3   0.2   0.05   0.1    0.025  0.78   0.78   0.1                            I-4   0.1   0.1    0.2    0.05   0.78   0.78   0.1                            I-5   0.39  1.56   0.78   0.39   3.13   12.5   0.1                            I-6   0.39  0.39   0.39   0.2    1.56   12.5   0.1                            I-7   0.2   0.39   0.2    0.05   0.39   0.78   0.05                           I-8   0.2   0.39   0.2    0.2    0.39   0.78   0.05                           I-9   0.1   0.2    0.2    0.1    3.13   1.56   0.78                           I-10  0.39  0.39   1.56   1.56   6.25   12.5   0.78                           I-11  0.1   0.1    0.2    0.05   1.56   1.56   0.39                           I-12  0.1   0.1    0.2    0.025  1.56   1.56   0.39                           I-13  0.39  1.56   1.56   0.78   1.56   3.13   0.78                           I-14  0.1   0.78   0.39   0.2    3.13   3.13   1.56                           I-15  0.1   0.2    0.78   0.39   1.56   1.56   0.39                           I-16  0.2   0.2    0.39   0.78   1.56   1.56   0.39                           I-18  0.1   0.2    0.2    0.2    1.56   --     --                             I-20  0.2   0.78   0.39   0.2    1.56   1.56   0.1                            I-21  0.39  0.2    0.1    0.025  6.25   3.13   0.1                            I-22  0.39  0.2    0.1    0.013  3.13   6.25   0.39                           I-23  0.2   0.1    0.1    0.2    1.56   1.56   0.2                            I-24  0.2   0.1    0.1    0.1    0.78   1.56   0.2                            I-25  0.2   0.78   0.78   0.2    0.39   6.25   0.39                           I-26  0.1   0.39   1.56   0.2    0.39   6.25   0.2                            I-27  0.2   0.2    0.2    0.2    0.78   --     0.39                           I-28  0.39  0.2    0.2    0.2    1.56   --     0.78                           I-29  0.39  0.78   0.78   0.39   3.13   1.56   0.39                           I-30  0.39  1.56   0.78   0.39   6.25   3.13   0.78                           I-31  0.2   0.39   0.78   0.39   0.78   0.78   0.39                           I-32  0.39  0.39   0.78   0.39   1.56   0.78   0.39                           I-33  0.78  0.78   1.56   0.39   3.13   3.13   1.56                           I-34  0.78  1.56   1.56   0.78   6.25   3.13   1.56                           I-35  0.39  0.78   0.78   0.39   0.78   1.56   0.78                           I-36  0.39  0.78   1.56   0.39   1.56   1.56   0.78                           I-37  0.2   0.39   0.78   0.2    0.2    --     0.78                           I-38  0.78  0.78   0.39   0.2    0.78   --     3.13                           I-39  0.2   0.39   0.2    0.2    0.2    --     0.78                           I-40  0.2   0.39   0.1    0.2    0.2    --     0.78                           I-41  0.2   0.78   0.78   0.39   3.13   3.13   6.25                           I-42  0.2   0.78   0.78   0.39   3.13   3.13   3.13                           I-43  0.1   0.1    0.1    0.05   0.78   1.56   0.78                           I-44  0.05  0.39   0.2    0.2    1.56   1.56   0.78                           I-45  0.1   0.2    0.78   0.39   1.56   3.13   0.78                           I-46  0.78  0.78   0.39   0.2    6.25   12.5   6.25                           I-47  0.2   0.2    0.78   0.1    1.56   6.25   1.56                           I-48  0.1   0.39   0.78   0.39   1.56   3.13   1.56                           I-49  0.39  1.56   1.56   0.78   1.56   1.56   1.56                           I-50  0.78  3.13   3.13   1.56   3.13   3.13   3.13                           I-51  0.78  3.13   1.56   1.56   1.56   0.78   0.78                           I-52  0.39  3.13   1.56   0.78   1.56   0.78   1.56                           I-53  0.39  3.13   1.56   0.39   1.56   --     1.56                           I-54  0.78  6.25   3.13   1.56   3.13   6.25   3.13                           I-55  0.2   1.56   0.78   0.2    0.39   0.78   0.39                           I-56  0.2   0.78   0.78   0.39   0.78   0.39   0.39                           I-57  0.78  6.25   6.25   1.56   0.78   0.78   0.39                           I-59  0.39  0.78   1.56   0.78   0.78   0.78   0.39                           I-61  3.13  1.56   1.56   0.39   1.56   3.13   3.13                           I-64  1.56  3.13   1.56   0.39   3.13   1.56   1.56                           I-65  0.39  1.56   1.56   0.39   1.56   --     1.56                           I-68  0.78  1.56   1.56   0.2    0.78   1.56   0.78                           CTX   0.2   0.78   0.78   0.39   1.56   0.78   0.39                           __________________________________________________________________________     *CTX: Cefotaxime                                                         

We claim:
 1. A cephalosporin compound of formula (I) ##STR8## wherein R₁is C₁₋₄ alkyl, C₃₋₄ alkenyl, C₃₋₄ alkynyl or --C(R^(a))(R^(b))CO₂ H,wherein R^(a) and R^(b), same or different, are a hydrogen atom or aC₁₋₄ alkyl group;R₂ is a C₁₋₄ alkyl, C₃₋₄ alkenyl, C₃₋₄ cycloalkyl orcarboxyalkyl; R₃ is selected from unsubstituted piperazine, piperazinesubstituted with a C₁₋₄ alkyl at the N-- or 2-position thereof,unsubstituted imidazole and imidazole substituted with C₁₋₄ alkyl; R₄ ishydrogen or carboxylic acid; or a pharmaceutically acceptable saltthereof.
 2. A process for preparing a cephalosporin compound of formula(I), or a pharmaceutically acceptable salt thereof, which comprisesreacting a compound of formula (III) with a compound of formula (III) inthe presence of a solvent; ##STR9## wherein R₁, R₂, R₃ and R₄ are thesame as defined in claim
 1. 3. A cephalosporin compound as recited inclaim 1, wherein:R₁ is selected from the group consisting of methyl,ethyl, allyl, propargyl, --C(CH₃)₂ CO₂ H and --CH₂ CO₂ H; R₂ is selectedfrom the group consisting of methyl, ethyl, allyl, cyclopropyl and --CH₂CO₂ H.
 4. The process for preparing a cephalosporin compound as recitedin claim 2, wherein:R₁ is selected from the group consisting of methyl,ethyl, allyl, propargyl, --C(CH₃)₂ CO₂ H and --CH₂ CO₂ H; R₂ is selectedfrom the group consisting of methyl, ethyl, allyl, cyclopropyl and --CH₂CO₂ H; R₃ is selected from unsubstituted piperazine, piperazinesubstituted with a C₁₋₄ alkyl at the N-- or 2-position thereof,unsubstituted imidazole and imidazole substituted with C₁₋₄ alkyl.